Modulation of CD8+ T Cell antitumor responses by EGFR-TKI in non-small cell lung cancer 2926

Abstract Description Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths globally. The primary treatment for NSCLC patients carrying EGFR mutations is EGFR tyrosine kinase inhibitors (EGFR-TKI). Although EGFR-TKIs have shown remarkable efficacy, their potential impact on the immune system remains unknown. Understanding the interactions between EGFR-TKIs and immune regulation is crucial for developing combination therapy strategies. Therefore, further investigation into the immunomodulatory effects of EGFR-TKIs is warranted. This study reveals that EGFR-TKIs could inhibit the activation and proliferation of CD8+ T cells and reduce the production of effector cytokines. Furthermore, combining EGFR-TKI with anti-PD-1 therapy yielded no synergistic benefit on tumor control and resulted in a lower frequency of IFNγ+ or GZMB+ CD8+ T cells compared to anti-PD-1 monotherapy. These findings were corroborated by analysis of peripheral blood samples from NSCLC patients receiving EGFR-TKI, which revealed decreased CD8+ T cell activation and IFNγ production. Additionally, we identified the target profile of EGFR-TKI in T cells by Target Identification by Specific Tagging and Antibody Detection (TISTA) approaches and LC-MS/MS analysis. Collectively, these findings suggest that EGFR-TKI exerts a suppressive effect on the effector function and antitumor response of CD8+ T cells. These findings provide vital information for developing therapeutic strategies for NSCLC patients. Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)